{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:28:33Z","timestamp":1790069313619,"version":"4.0.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":279,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GTN2009264"],"award-info":[{"award-number":["GTN2009264"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003792","name":"Brain Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012599","name":"Bethlehem Griffiths Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012599","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARG-NTF-22-971405"],"award-info":[{"award-number":["AARG-NTF-22-971405"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health and Medical Research Council Investigator"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Plasma biomarkers are promising for detecting Alzheimer\u2019s disease (AD) pathology, but their role in cognitively healthy individuals remains unclear. Plasma pTau-217 has high diagnostic accuracy for clinical and prodromal AD, yet its relevance in preclinical stages is underexplored. We examined if plasma biomarkers of AD, neurodegeneration, and neuroinflammation were associated with cognition, brain structure, and their cerebrospinal fluid (CSF) counterparts in dementia-free older adults. We studied community-based, dementia-free older adults from the Brain and Cognitive Health (BACH) cohort. Neuropsychological testing assessed global cognition (MMSE), memory (Logical Memory II), visual processing (Hooper Visual Organization Test), processing speed (Trail Making Test-A), and reasoning (Similarities). Paired plasma and CSF biomarkers [phosphorylated Tau-217 (pTau-217), phosphorylated Tau-181 (pTau-181), Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid-beta 42\/40 (A\u03b242\/40)] were measured using Single molecule arrays (SIMOA). Brain magnetic resonance imaging (MRI)-derived cortical thickness was used as a neurodegeneration marker. Multivariable linear regression assessed associations between log10-transformed plasma biomarker levels, cognition (adjusted for age, sex, education, hypertension, hyperlipidemia, diabetes), and cortical thickness (adjusted for age, sex, education, and intracranial volume). Pearson\u2019s correlations and Bland-Altman plots evaluated plasma-CSF agreement. There were 147 dementia-free participants [mean age \u00b1 standard deviation (SD): 66.7 \u00b1 7.7 years; 56% women]. Higher plasma pTau-217 levels associated with lower global cognition scores (\u03b2 \u22120.80, 95% C.I. \u22121.56, \u22120.03, P = 0.041) and abstract reasoning [\u03b2 \u22120.86, 95% confidence interval (C.I.) \u22121.62, \u22120.09, P = 0.028]. Greater plasma pTau-217 also associated with lower global cortical thickness [\u03b2eta (\u03b2) \u22120.21, 95% confidence interval (C.I). \u22120.37, \u22120.06, per log unit change; P = 0.006]. Nfl associated with memory (\u03b2 \u22121.38, 95% C.I. \u22122.65, \u22120.12, P = 0.033), while GFAP associated with global cognition (\u03b2 \u22121.48, 95% C.I. \u22122.44, \u22120.52, P = 0.003) and memory (\u03b2 \u22121.05, 95% C.I. \u22122.05, \u22120.04, P = 0.041). No associations were found between the plasma biomarkers and processing speed or visual processing (P &amp;gt; 0.05 for all). Among 47 participants with paired plasma-CSF biomarkers, plasma pTau-217 showed the strongest correlation with its CSF counterpart (R = 0.76, P &amp;lt; 0.0001), followed by GFAP (R = 0.66, P &amp;lt; 0.0001), pTau-181 (R = 0.61, P &amp;lt; 0.0001), NfL (R = 0.56, P &amp;lt; 0.0001), and A\u03b242\/40 (R = 0.53, P = 0.0001). In conclusion, plasma pTau-217 levels were associated with both cognition and cortical thickness in dementia-free older adults. All plasma biomarkers correlated significantly with their CSF counterpart. These findings reinforce the utility of plasma biomarkers, particularly pTau-217, as indicators of neurodegenerative processes, even in asymptomatic individuals.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf383","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T12:05:48Z","timestamp":1759406748000},"source":"Crossref","is-referenced-by-count":10,"title":["Plasma phosphorylated tau-217 correlates with brain atrophy, cognition, and cerebrospinal fluid biomarkers in a cognitively healthy community cohort"],"prefix":"10.1093","volume":"7","author":[{"given":"Ming Ann","family":"Sim","sequence":"first","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"},{"name":"Department of Intensive Care Medicine, Ng Teng Fong General Hospital and Department of Anesthesia, National University of Singapore , Singapore 119074 , Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4882-4183","authenticated-orcid":false,"given":"Ella","family":"Rowsthorn","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"},{"name":"Department of Neuroscience, The School of Translational Medicine, Monash University , Melbourne 3004 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Neurology, Alfred Health , Melbourne 3004 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mujun","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"},{"name":"Department of Neuroscience, The School of Translational Medicine, Monash University , Melbourne 3004 , Australia"},{"name":"Department of Neurology, Alfred Health , Melbourne 3004 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lachlan","family":"Cribb","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Franks","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, The School of Translational Medicine, Monash University , Melbourne 3004 , Australia"},{"name":"Department of Neurology, Alfred Health , Melbourne 3004 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Yiallourou","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Cavuoto","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"},{"name":"Department of Neurology, Alfred Health , Melbourne 3004 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian H","family":"Harding","sequence":"additional","affiliation":[{"name":"Department of Neurology, Alfred Health , Melbourne 3004 , Australia"},{"name":"QIMR Berghofer Medical Research Institute , Herston, Queensland 4006 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-3811","authenticated-orcid":false,"given":"Trevor T J","family":"Chong","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"},{"name":"Department of Neuroscience, The School of Translational Medicine, Monash University , Melbourne 3004 , Australia"},{"name":"Department of Clinical Neurosciences, St Vincent\u2019s Hospital , Melbourne 3065 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Law","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"},{"name":"Department of Neuroscience, The School of Translational Medicine, Monash University , Melbourne 3004 , Australia"},{"name":"Department of Neurology, Alfred Health , Melbourne 3004 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence J","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"},{"name":"Department of Neuroscience, The School of Translational Medicine, Monash University , Melbourne 3004 , Australia"},{"name":"Department of Neurology, Alfred Health , Melbourne 3004 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-0907","authenticated-orcid":false,"given":"Lucy","family":"Vivash","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"},{"name":"Department of Neuroscience, The School of Translational Medicine, Monash University , Melbourne 3004 , Australia"},{"name":"Department of Neurology, Alfred Health , Melbourne 3004 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P","family":"Pase","sequence":"additional","affiliation":[{"name":"School of Psychological Science and Turner Institute for Brain and Mental Health, Monash University , Melbourne, Clayton 3800 , Australia"},{"name":"Department of Neuroscience, The School of Translational Medicine, Monash University , Melbourne 3004 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"issue":"10","key":"2025102405514195200_fcaf383-B1","doi-asserted-by":"crossref","first-page":"4729","DOI":"10.1002\/alz.13084","article-title":"Plasma ATN(I) classification and precision pharmacology in Alzheimer's disease","volume":"19","author":"Imbimbo","year":"2023","journal-title":"Alzheimers 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